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Long noncoding RNA GAS5 affects cell proliferation and predicts a poor prognosis in patients with colorectal cancer

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Abstract

Colorectal cancer (CRC) is the third most common type of cancer worldwide. Recent studies have shown that lncRNAs play important roles in carcinogenesis. The aim of this study was to explore the role of lncRNA GAS5 in CRC. Real-time PCR was performed to investigate the expression of GAS5 in tumor tissues and corresponding non-tumor colorectal tissues from 66 patients with CRC. The lower expression of GAS5 was significantly correlated with large tumor size, low histological grade and advanced TNM stage. Multivariate analyses revealed that GAS5 expression served as an independent predictor for overall survival (P = 0.034). Further experiments revealed that overexpressed GAS5 significantly repressed the proliferation both in vitro and in vivo. In conclusion, our results suggest that GAS5, as a growth regulator, may serve as a candidate prognostic biomarker in human colorectal cancer.

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References

  1. Reissfelder C, Timke C, Schmitz-Winnenthal H, Rahbari NN, Koch M, Klug F, Roeder F, Edler L, Debus J, Buchler MW, et al. A randomized controlled trial to investigate the influence of low dose radiotherapy on immune stimulatory effects in liver metastases of colorectal cancer. BMC Cancer. 2011;11:419.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Reissfelder C, Rahbari NN, Koch M, Ulrich A, Pfeilschifter I, Waltert A, Muller SA, Schemmer P, Buchler MW, Weitz J. Validation of prognostic scoring systems for patients undergoing resection of colorectal cancer liver metastases. Ann Surg Oncol. 2009;16(12):3279–88.

    Article  PubMed  Google Scholar 

  3. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59(4):225–49.

    Article  PubMed  Google Scholar 

  4. Rupnarain C, Dlamini Z, Naicker S, Bhoola K. Colon cancer: genomics and apoptotic events. Biol Chem. 2004;385(6):449–64.

    Article  PubMed  CAS  Google Scholar 

  5. Calvert PM, Frucht H. The genetics of colorectal cancer. Ann Intern Med. 2002;137(7):603–12.

    Article  PubMed  CAS  Google Scholar 

  6. Spizzo R, Almeida MI, Colombatti A, Calin GA. Long non-coding RNAs and cancer: a new frontier of translational research? Oncogene. 2012;31(43):4577–87.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  7. Yang F, Zhang L, Huo XS, Yuan JH, Xu D, Yuan SX, Zhu N, Zhou WP, Yang GS, Wang YZ, et al. Long noncoding RNA high expression in hepatocellular carcinoma facilitates tumor growth through enhancer of zeste homolog 2 in humans. Hepatology. 2011;54(5):1679–89.

    Article  PubMed  CAS  Google Scholar 

  8. Cui Z, Ren S, Lu J, Wang F, Xu W, Sun Y, Wei M, Chen J, Gao X, Xu C, et al. The prostate cancer-up-regulated long noncoding RNA PlncRNA-1 modulates apoptosis and proliferation through reciprocal regulation of androgen receptor. Urol Oncol. 2013;31(7):1117–23.

    Article  PubMed  CAS  Google Scholar 

  9. Geng YJ, Xie SL, Li Q, Ma J, Wang GY. Large intervening non-coding RNA HOTAIR is associated with hepatocellular carcinoma progression. J Int Med Res. 2011;39(6):2119–28.

    Article  PubMed  CAS  Google Scholar 

  10. Shi X, Sun M, Liu H, Yao Y, Kong R, Chen F, Song Y. A critical role for the long non-coding RNA GAS5 in proliferation and apoptosis in non-small-cell lung cancer. Mol Carcinog. 2013.

  11. Lu KH, Li W, Liu XH, Sun M, Zhang ML, Wu WQ, Xie WP, Hou YY. Long non-coding RNA MEG3 inhibits NSCLC cells proliferation and induces apoptosis by affecting p53 expression. BMC Cancer. 2013;13:461.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Zhang EB, Kong R, Yin DD, You LH, Sun M, Han L, Xu TP, Xia R, Yang JS, De W, et al. Long noncoding RNA ANRIL indicates a poor prognosis of gastric cancer and promotes tumor growth by epigenetically silencing of miR-99a/miR-449a. Oncotarget. 2014;5(8):2276–92.

    PubMed  PubMed Central  Google Scholar 

  13. Zhang EB, Yin DD, Sun M, Kong R, Liu XH, You LH, Han L, Xia R, Wang KM, Yang JS, et al. P53-regulated long non-coding RNA TUG1 affects cell proliferation in human non-small cell lung cancer, partly through epigenetically regulating HOXB7 expression. Cell Death Dis. 2014;5:e1243.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  14. Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464(7291):1071–6.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  15. Kim K, Jutooru I, Chadalapaka G, Johnson G, Frank J, Burghardt R, Kim S, Safe S. HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer. Oncogene. 2013;32(13):1616–25.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  16. Zhou Y, Zhang X, Klibanski A. MEG3 noncoding RNA: a tumor suppressor. J Mol Endocrinol. 2012;48(3):R45–53.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  17. Benetatos L, Vartholomatos G, Hatzimichael E. MEG3 imprinted gene contribution in tumorigenesis. Int J Cancer. 2011;129(4):773–9.

    Article  PubMed  CAS  Google Scholar 

  18. Kino T, Hurt DE, Ichijo T, Nader N, Chrousos GP. Noncoding RNA gas5 is a growth arrest- and starvation-associated repressor of the glucocorticoid receptor. Sci Signal. 2010;3(107):ra8.

    PubMed  PubMed Central  Google Scholar 

  19. Schneider C, King RM, Philipson L. Genes specifically expressed at growth arrest of mammalian cells. Cell. 1988;54(6):787–93.

    Article  PubMed  CAS  Google Scholar 

  20. Pickard MR, Mourtada-Maarabouni M, Williams GT. Long non-coding RNA GAS5 regulates apoptosis in prostate cancer cell lines. Biochim Biophys Acta. 2013;1832(10):1613–23.

    Article  PubMed  CAS  Google Scholar 

  21. Qiao HP, Gao WS, Huo JX, Yang ZS. Long non-coding RNA GAS5 functions as a tumor suppressor in renal cell carcinoma. Asian Pac J Cancer Prev. 2013;14(2):1077–82.

    Article  PubMed  Google Scholar 

  22. Mourtada-Maarabouni M, Pickard MR, Hedge VL, Farzaneh F, Williams GT. GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer. Oncogene. 2009;28(2):195–208.

    Article  PubMed  CAS  Google Scholar 

  23. Mourtada-Maarabouni M, Hedge VL, Kirkham L, Farzaneh F, Williams GT. Growth arrest in human T-cells is controlled by the non-coding RNA growth-arrest-specific transcript 5 (GAS5). J Cell Sci. 2008;121(Pt 7):939–46.

    Article  PubMed  CAS  Google Scholar 

  24. Birney E, Stamatoyannopoulos JA, Dutta A, Guigo R, Gingeras TR, Margulies EH, Weng Z, Snyder M, Dermitzakis ET, Thurman RE, et al. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. 2007;447(7146):799–816.

    Article  PubMed  CAS  Google Scholar 

  25. Louro R, Smirnova AS, Verjovski-Almeida S. Long intronic noncoding RNA transcription: expression noise or expression choice? Genomics. 2009;93(4):291–8.

    Article  PubMed  CAS  Google Scholar 

  26. Amaral PP, Dinger ME, Mercer TR, Mattick JS. The eukaryotic genome as an RNA machine. Science. 2008;319(5871):1787–9.

    Article  PubMed  CAS  Google Scholar 

  27. Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 2009;458(7235):223–7.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  28. Michalik KM, You X, Manavski Y, Doddaballapur A, Zornig M, Braun T, John D, Ponomareva Y, Chen W, Uchida S, et al. Long noncoding RNA MALAT1 regulates endothelial cell function and vessel growth. Circ Res. 2014;114(9):1389–97.

    Article  PubMed  CAS  Google Scholar 

  29. Zhang EB, Yin DD, Sun M, Kong R, Liu XH, You LH, Han L, Xia R, Wang KM, Yang JS, et al. P53-regulated long non-coding RNA TUG1 affects cell proliferation in human non-small cell lung cancer, partly through epigenetically regulating HOXB7 expression. Cell Death Dis. 2014;5:e1243.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  30. Ying L, Chen Q, Wang Y, Zhou Z, Huang Y, Qiu F. Upregulated MALAT-1 contributes to bladder cancer cell migration by inducing epithelial-to-mesenchymal transition. Mol BioSyst. 2012;8(9):2289–94.

    Article  PubMed  CAS  Google Scholar 

  31. Nie L, Wu HJ, Hsu JM, Chang SS, Labaff AM, Li CW, Wang Y, Hsu JL, Hung MC. Long non-coding RNAs: versatile master regulators of gene expression and crucial players in cancer. Am J Transl Res. 2012;4(2):127–50.

    PubMed  CAS  PubMed Central  Google Scholar 

  32. Prensner JR, Rubin MA, Wei JT, Chinnaiyan AM. Beyond PSA: the next generation of prostate cancer biomarkers. Sci Transl Med. 2012;4(127):127rv123.

    Article  Google Scholar 

  33. Salagierski M, Schalken JA. Molecular diagnosis of prostate cancer: pCA3 and TMPRSS2:ERG gene fusion. J Urol. 2012;187(3):795–801.

    Article  PubMed  CAS  Google Scholar 

  34. Yang Z, Zhou L, Wu LM, Lai MC, Xie HY, Zhang F, Zheng SS. Overexpression of long non-coding RNA HOTAIR predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation. Ann Surg Oncol. 2011;18(5):1243–50.

    Article  PubMed  Google Scholar 

  35. Garcia-Claver A, Lorente M, Mur P, Campos-Martin Y, Mollejo M, Velasco G, Melendez B. Gene expression changes associated with erlotinib response in glioma cell lines. Eur J Cancer. 2013;49(7):1641–53.

    Article  PubMed  CAS  Google Scholar 

  36. Sun M, Jin FY, Xia R, Kong R, Li JH, Xu TP, Liu YW, Zhang EB, Liu XH, De W. Decreased expression of long noncoding RNA GAS5 indicates a poor prognosis and promotes cell proliferation in gastric cancer. BMC Cancer. 2014;14:319.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Tu ZQ, Li RJ, Mei JZ, Li XH. Down-regulation of long non-coding RNA GAS5 is associated with the prognosis of hepatocellular carcinoma. Int J Clin Exp Pathol. 2014;7(7):4303–9.

    PubMed  PubMed Central  Google Scholar 

  38. Zhang Z, Zhu Z, Watabe K, Zhang X, Bai C, Xu M, Wu F, Mo YY. Negative regulation of lncRNA GAS5 by miR-21. Cell Death Differ. 2013;20(11):1558–68.

    Article  PubMed  CAS  Google Scholar 

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Conflict of interest

The authors have declared that no conflicts of interest exist.

Author information

Authors and Affiliations

  1. Cancer Research and Therapy Center, The Second Affiliated Hospital of Southeast University, Nanjing, Jiangsu, China

    Dandan Yin

  2. Departments of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China

    Dandan Yin, Xuezhi He, Erbao Zhang, Wei De & Zhihong Zhang

  3. Laboratory Center, Subei People’s Hospital, Yangzhou, Jiangsu, China

    Rong Kong

  4. Departments of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

    Zhihong Zhang

Authors
  1. Dandan Yin
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  2. Xuezhi He
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  4. Rong Kong
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  5. Wei De
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  6. Zhihong Zhang
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Correspondence to Wei De or Zhihong Zhang.

Additional information

Dandan Yin, Xuezhi He, and Erbao Zhang contributed equally to this work and should be regarded as joint first authors.

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Yin, D., He, X., Zhang, E. et al. Long noncoding RNA GAS5 affects cell proliferation and predicts a poor prognosis in patients with colorectal cancer. Med Oncol 31, 253 (2014). https://doi.org/10.1007/s12032-014-0253-8

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  • DOI: https://doi.org/10.1007/s12032-014-0253-8

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